Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness...Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness,results in latency.Reactivation of latent HHV-6 is common after liver transplantation.Since the majority of human beings harbor the latent virus,HHV-6 infections after liver transplantation are most probably caused by end ogenous reactivation or superinfection.In a minority of cases,primary HHV-6 infection may occur when an HHV-6-seronegative individual receives a liver allograft from an HHV-6-seropositive donor.The vast major ity of HHV-6 infections after liver transplantation are asy-mptomatic.Only in a minority of cases,when HHV-6 causes a febrile illness associated with rash and mye- losuppression,hepatitis,gastroenteritis,pneumonitis,and encephalitis after liver transplantation.In addition,HHV-6 has been implicated in a variety of indirect effects,such as allograft rejection and increased predis- pos ition to and severity of other infections,includingcytomegalovirus,hepatitis C virus,and opportunistic fungi.Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6,there is currently no recommended HHV-6-specific approach prevention after liver transplantation.Asymptomatic HHV-6 infection does not require antiviral treatment,while treatment of established HHV-6 disease is treated with intravenous ganciclovir,foscarnet,or cidofovir and this should be com plemented by a reduction in immunosuppression.展开更多
The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-29...The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-297). We have previously shown that the sialic acid-containing (Sia<sup>+</sup>) fraction of intravenous immune globulin (IVIG) influences cell surface marker expression and cytokine/ chemokine secretion during the differentiation and maturation of human dendritic cells (DC). The present study examined the effects of Sia<sup>+</sup> IgG on human peripheral blood mononuclear cell (PBMC)-derived monocyte and macrophage surface marker expression and cytokine/chemokine secretion. Sia<sup>+</sup> IgG induced increased expression of CD80 and dendritic cell immunoreceptor (DCIR) on monocytes, whereas the expression of HLA-DR was decreased. In addition, the production of IL-6, TNFα, IL-1β, and CXCL1 by monocytes was profoundly increased by treatment with Sia<sup>+</sup> IgG. Sia<sup>+</sup> IgG also increased the expression of cell surface markers associated with macrophage polarization (e.g. CD40 and CD206) on monocytes. In macrophage-colony stimulating factor (MCSF) generated macrophages, Sia<sup>+</sup> IgG induced increased production of numerous cytokines/ chemokines including IL-6, TNFα, CXCL1, and IL-10, and the expression of the macrophage surface marker CD163. Our data extended prior observations of Sia<sup>+</sup> IgG on DC function and showed that Sia<sup>+</sup> IgG was able to differentially modulate multiple pathways in monocytes and macrophages. Our data indicate that the Sia<sup>+</sup> fraction of IVIG possesses the ability to influence inflammatory processes in multiple immune cell types and induces novel signatures in cell surface marker expression and cytokine/chemokine production.展开更多
Liver disease accounts for approximately 2 million deaths per year worldwide,including 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma(HCC)(1).Liver transp...Liver disease accounts for approximately 2 million deaths per year worldwide,including 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma(HCC)(1).Liver transplantation(LTx)is the definitive management for end-stage liver disease and HCC in both children and adults.However,the number of liver transplant candidates on the waiting list exceeds that of available allografts.Approximately one-third of the global population has serological evidence of past or current hepatitis B virus(HBV)infection,including 250 million people with chronic HBV infection.The concept of using HBV-positive liver allografts has been implemented to expand the organ pool worldwide(2).Especially in regions with high or intermediate prevalence of HBV infection,these allografts can be an optimal choice for LTx recipients.Over the decades,LTx from HBV-exposed allografts has shifted from the first case in the 1980s to expanded practice supported by positive outcomes,particularly with the availability of safe and effective clinical therapies(3).展开更多
Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the respons...Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the responses to type I interferon(IFN-I),promotes B cells antigen presentation and activation,subsequently enhances anti-tumour responses of CD4^(+) and CD8^(+)T cells and inhibits tumour growth.This study provides important implications for anti-tumour therapy.展开更多
文摘Human herpes virus 6 (HHV-6) infects > 95% of humans.Primary infection which occurs mostly during the f irst 2 years of life in the form of roseola infantum,non-spe cif ic febrile illness,or an asymptomatic illness,results in latency.Reactivation of latent HHV-6 is common after liver transplantation.Since the majority of human beings harbor the latent virus,HHV-6 infections after liver transplantation are most probably caused by end ogenous reactivation or superinfection.In a minority of cases,primary HHV-6 infection may occur when an HHV-6-seronegative individual receives a liver allograft from an HHV-6-seropositive donor.The vast major ity of HHV-6 infections after liver transplantation are asy-mptomatic.Only in a minority of cases,when HHV-6 causes a febrile illness associated with rash and mye- losuppression,hepatitis,gastroenteritis,pneumonitis,and encephalitis after liver transplantation.In addition,HHV-6 has been implicated in a variety of indirect effects,such as allograft rejection and increased predis- pos ition to and severity of other infections,includingcytomegalovirus,hepatitis C virus,and opportunistic fungi.Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6,there is currently no recommended HHV-6-specific approach prevention after liver transplantation.Asymptomatic HHV-6 infection does not require antiviral treatment,while treatment of established HHV-6 disease is treated with intravenous ganciclovir,foscarnet,or cidofovir and this should be com plemented by a reduction in immunosuppression.
文摘The effector functions elicited by the fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibodies are subject to variation by the presence of terminal sialic acid (Sia) residues at asparagine-297 (Asn-297). We have previously shown that the sialic acid-containing (Sia<sup>+</sup>) fraction of intravenous immune globulin (IVIG) influences cell surface marker expression and cytokine/ chemokine secretion during the differentiation and maturation of human dendritic cells (DC). The present study examined the effects of Sia<sup>+</sup> IgG on human peripheral blood mononuclear cell (PBMC)-derived monocyte and macrophage surface marker expression and cytokine/chemokine secretion. Sia<sup>+</sup> IgG induced increased expression of CD80 and dendritic cell immunoreceptor (DCIR) on monocytes, whereas the expression of HLA-DR was decreased. In addition, the production of IL-6, TNFα, IL-1β, and CXCL1 by monocytes was profoundly increased by treatment with Sia<sup>+</sup> IgG. Sia<sup>+</sup> IgG also increased the expression of cell surface markers associated with macrophage polarization (e.g. CD40 and CD206) on monocytes. In macrophage-colony stimulating factor (MCSF) generated macrophages, Sia<sup>+</sup> IgG induced increased production of numerous cytokines/ chemokines including IL-6, TNFα, CXCL1, and IL-10, and the expression of the macrophage surface marker CD163. Our data extended prior observations of Sia<sup>+</sup> IgG on DC function and showed that Sia<sup>+</sup> IgG was able to differentially modulate multiple pathways in monocytes and macrophages. Our data indicate that the Sia<sup>+</sup> fraction of IVIG possesses the ability to influence inflammatory processes in multiple immune cell types and induces novel signatures in cell surface marker expression and cytokine/chemokine production.
基金supported by the Sichuan Science and Technology Program(2019YFG0036)the Major National Science and Technology Special Projects(No.2017ZX10203205-005-002 and No.2017ZX10203205-001-004)the National Natural Science Foundation of China(No.81470037 and No.81770653).
文摘Liver disease accounts for approximately 2 million deaths per year worldwide,including 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma(HCC)(1).Liver transplantation(LTx)is the definitive management for end-stage liver disease and HCC in both children and adults.However,the number of liver transplant candidates on the waiting list exceeds that of available allografts.Approximately one-third of the global population has serological evidence of past or current hepatitis B virus(HBV)infection,including 250 million people with chronic HBV infection.The concept of using HBV-positive liver allografts has been implemented to expand the organ pool worldwide(2).Especially in regions with high or intermediate prevalence of HBV infection,these allografts can be an optimal choice for LTx recipients.Over the decades,LTx from HBV-exposed allografts has shifted from the first case in the 1980s to expanded practice supported by positive outcomes,particularly with the availability of safe and effective clinical therapies(3).
基金the Key Research and Development Project of Sichuan Provincial Science and Technology Department(No.23ZDYF2875).
文摘Recently,Lloyd Bod et al.published a study in Nature that identified the B-cell immune checkpoint T cell immunoglobulin and mucin domain 1(TIM-1)and mechanistically elucidated that targeting TIM-1 enhances the responses to type I interferon(IFN-I),promotes B cells antigen presentation and activation,subsequently enhances anti-tumour responses of CD4^(+) and CD8^(+)T cells and inhibits tumour growth.This study provides important implications for anti-tumour therapy.
